Childhood glaucoma is a rare disorder that occurs from birth until teenage years caused by an abnormality of aqueous humor pathways. About 50-70% of Peters\' anomaly is accompanied by secondary childhood glaucoma. The presence of glaucoma will affect the prognosis. We reported the evaluation and treatment of secondary childhood glaucoma due to Peters\' anomaly. A 5 months-old boy was presented with the complaint of a enlarged left eye since 3 months old. The complaint was accompanied by a watering eye and frequently closed upon light exposure. The left eye looked opaquer than contralateral. Examination under anesthesia showed that the intraocular pressure (IOP) was 35 mmHg in the left eye and the corneal diameter was 14 mm. Other findings were keratopathy, diffuse corneal edema, buphthalmos, shallow anterior chamber, anterior synechiae, and linear slit shaped pupils in the nasal region. Patient was treated with ophthalmic timolol maleate which was later followed by trabeculectomy. After 1 week post-surgery, IOP assessment by palpation suggested the right eye within normal range while the IOP of left eye was higger than normal. Blepharospasm, epiphora, photophobia, bleb on superior, subconjunctiva bleeding, buphthalmos, keratopathy, minimal corneal edema, anterior chamber with shallow image, and posterior synechia were found in left eye anterior segment. In conclusion, trabeculotomy and trabeculectomy are recommended if there is no reduction of IOP observed after receiving timolol maleate therapy. The choice of surgical management is dependent on the feasibility of the protocol.

OBJECTIVE: To describe three anterior segment dysgenesis disorders with infantile corneal opacities, namely, congenital hereditary endothelial dystrophy (CHED), primary congenital glaucoma (PCG), and Peters anomaly (PA) in terms of clinical characteristics, histopathology, genetic association, and diagnostic imaging profiles using imaging modalities such as ultrasound biomicroscopy (UBM) and microscope-integrated intraoperative optical coherence tomography (i-OCT).
METHODS: Seventy-four eyes with 22 eyes of CHED, 28 eyes of PA, and 24 eyes of PCG were clinically evaluated and underwent imaging using UBM and i-OCT. Corneal buttons of 16 operated patients underwent histopathological analysis, while genetic analysis was done in 23 patients using whole-exome sequencing.
RESULTS: Corneal diameters (CD) and UBM parameters like anterior chamber depth (ACD), iris thickness (IT), and ciliary body (CB) thickness revealed a statistically significant difference between the three categories. In PA, 9 eyes had a third rare phenotype with only a posterior corneal defect with no iris adhesions. Genetic mutations were seen in all tested patients with CHED, in 83.3% of patients with PCG, and in 80% of patients with the third type of PA. i-OCT helped in the characterization of corneal opacity, identification of posterior corneal defects, iridocorneal adhesions, and contour of Descemet\'s membrane.
CONCLUSIONS: Overlapping phenotypes of the above disorders cause a diagnostic dilemma and parameters like CDs, UBM ACD, IT, and CB thickness help differentiate between them. i-OCT can help in classifying the diseases in a high resolution, non-contact manner, and can better delineate corneal characteristics. The rare third type of PA phenotype may have a genetic association.

Glaucoma secondary to Peters anomaly is an important factor affecting visual prognosis, but there are few reports on the condition. This study aimed to investigate the characteristics of glaucoma associated with Peters anomaly and glaucoma surgery outcomes. This retrospective study included 31 eyes of 20 patients with Peters anomaly. Peters anomaly was classified into three stages: Stage 1, with a posterior corneal defect only; Stage 2, a corneal defect with iridocorneal adhesion; and Stage 3, a corneal defect with lens abnormalities. The associations between glaucoma and anterior segment dysgenesis severity, visual prognosis, and glaucoma surgery outcomes were analyzed. Sixteen eyes of ten patients developed glaucoma. Stage 1 Peters anomaly had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Of the 16 eyes with glaucoma, 11 underwent surgery. Eight of these eleven eyes achieved intraocular pressure (IOP) control. Five of the nine eyes that underwent trabeculotomy (TLO) succeeded, and none had corneal staphyloma. Three of the four eyes for which TLO was ineffective had corneal staphyloma (p = 0.0331). Patients with Peters anomaly are more likely to develop glaucoma as anterior segment dysgenesis progresses, and the effect of TLO is limited if corneal staphyloma is present.

UNASSIGNED: To report a case of Axenfeld-Rieger and Stickler Syndrome in a pediatric patient.
UNASSIGNED: A 3-month-old male was referred to the glaucoma clinic after he was noted to have elevated intraocular pressures in both eyes. His family history was notable for infantile glaucoma on his maternal side and retinal detachment on his paternal side. He was found to have anterior segment dysgenesis with iris strands, iridocorneal adhesions, and corectopia, as well as veil-like vitreous in both eyes. He required trabeculotomy, goniotomy, and multiple Baerveldt glaucoma implants in both eyes to achieve intraocular pressure control. Furthermore, the patient later developed macula-involving retinal detachments in both eyes, requiring pars plana vitrectomy with silicone oil tamponade. Genetic analysis confirmed heterozygous pathogenic variants in both the FOXC1 and COL2A1 genes, leading to the concurrent diagnoses of Axenfeld-Rieger and Stickler syndromes.
UNASSIGNED: This is a rare case of a patient with concurrent Axenfeld-Rieger and Stickler syndromes. The severity of pathology in both the anterior and posterior segments required a collaborative multidisciplinary approach. In the diagnostic evaluation of congenital eye diseases, if there is strong family history of atypical findings for a given diagnosis, concurrent syndromes should be considered and ruled out. A comprehensive eye genetics panel may be a useful tool in these cases.

BACKGROUND: According to previous reports, PAX6-associated foveal hypoplasia (FH) could usually be accompanied by various anterior segment anomalies including variable iris changes. This study aims to exhibit unusual phenotypes of a novel missense variant of PAX6 from a Chinese pedigree.
METHODS: Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation.
RESULTS: WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye.
CONCLUSIONS: A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.

The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD).
To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions.
A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by CLIA-certified commercial genetic testing laboratories. Other co-authors were surveyed with respect to genetic panels used for the indications of interest. Ophthalmic panels were then compared using Concert Genetics in addition to their own websites.
Panels from each clinical category were included and summarized. This comparison highlighted the differences and similarities between panels so that clinicians can make informed decisions.
Access to genetic testing is increasing. The diagnostic yield of genetic testing is increasing. Each panel is different, so phenotyping or characterizing clinical characteristics that may help predict a specific genotype, as well as pre-test hypotheses regarding a genotype, should shape the choice of panels.

The Multidisciplinary Ophthalmic Genetics Clinic (MOGC) at the University of Michigan Kellogg Eye Center aims to provide medical and ophthalmic genetics care to patients with inherited ocular conditions. We have developed a clinical and referral workflow where each patient undergoes coordinated evaluation by our multidisciplinary team followed by discussions on diagnosis, prognosis, and genetic testing. Testing approaches are specific to each patient and can be targeted (single-gene, gene panel), broad (chromosomal microarray, whole-exome sequencing), or a combination. We hypothesize that this clinic model improves patient outcomes and quality of care. A retrospective chart review of patients in the MOGC from July 2020 to October 2022 revealed that the most common referral diagnoses were congenital cataracts, optic neuropathy, and microphthalmia, with 52% syndromic cases. Within this patient cohort, we saw a 76% uptake for genetic testing, among which 33% received a diagnostic test result. Our results support a tailored approach to genetic testing for specific conditions. Through case examples, we highlight the power and impact of our clinic. By integrating ophthalmic care with medical genetics and counseling, the MOGC has not only helped solve individual patient diagnostic challenges but has aided the greater population in novel genetic discoveries and research towards targeted therapeutics.

Hereditary causes are an important etiological category of childhood blindness. This study reports the real-world experience of a developing ocular genetic service.
The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North-West India. Children presenting to the genetic clinic with congenital or late-onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel-based sequencing/chromosomal microarray) was outsourced to third-party laboratories with the cost of the test being borne by the patient.
Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing.
Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Glaucoma in infancy and childhood is a rare disease. An immediate diagnosis and treatment are absolutely necessary to prevent blindness of affected children. Childhood glaucoma is characterized by a heterogeneous phenotype: besides primary congenital glaucoma, secondary types often exist and the individualized treatment requires an experienced interdisciplinary team. The pathogenesis is not always discernible and genetic alterations sometimes cause the disease. A surgical procedure is usually necessary to lower the intraocular pressure. Refractive and orthoptic care are equally important to avoid amblyopia. This article gives an overview of childhood glaucoma and outlines the most important diagnostic and therapeutic aspects.
UNASSIGNED: Das Glaukom im Säuglings- und Kindesalter ist eine seltene Erkrankung. Eine schnelle Diagnosestellung und Therapie sind zur Verhinderung einer Erblindung unbedingt erforderlich. Der Phänotyp ist heterogen: Neben primär kongenitalen Glaukomen bestehen häufig sekundäre Formen, deren Behandlung individuell ist und ein erfahrenes, interdisziplinäres Team erfordert. Die Pathogenese ist nicht immer klar, manchmal finden sich genetische Veränderungen. Therapeutisch ist in aller Regel eine Operation notwendig. Genauso wichtig ist eine gute orthoptische Anbindung zur Vermeidung sekundärer Amblyopie. Dieser Beitrag vermittelt einen Überblick über Glaukome im Kindesalter und umreißt die wichtigsten diagnostischen und therapeutischen Aspekte.

Ocular anterior segment dysgenesis (ASD) refers to a collection of developmental disorders affecting the anterior structures of the eye. Although a number of genes have been implicated in the etiology of ASD, the underlying pathogenetic mechanisms remain unclear. Mutations in genes encoding collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause Gould syndrome, a multi-system disorder that often includes ocular manifestations such as ASD and glaucoma. COL4A1 and COL4A2 are abundant basement membrane proteins that provide structural support to tissues and modulate signaling through interactions with other extracellular matrix proteins, growth factors, and cell surface receptors. In this study, we used a combination of histological, molecular, genetic and pharmacological approaches to demonstrate that altered TGFβ signaling contributes to ASD in mouse models of Gould syndrome. We show that TGFβ signaling was elevated in anterior segments from Col4a1 mutant mice and that genetically reducing TGFβ signaling partially prevented ASD. Notably, we identified distinct roles for TGFβ1 and TGFβ2 in ocular defects observed in Col4a1 mutant mice. Importantly, we show that pharmacologically promoting type IV collagen secretion or reducing TGFβ signaling ameliorated ocular pathology in Col4a1 mutant mice. Overall, our findings demonstrate that altered TGFβ signaling contributes to COL4A1-related ocular dysgenesis and implicate this pathway as a potential therapeutic target for the treatment of Gould syndrome.